The detection of the level of analytes, such as glucose, lactate, oxygen, and the like, in certain individuals is vitally important to their health. For example, the monitoring of glucose is particularly important to individuals with diabetes. Measurement of glucose levels is an essential part of diabetes treatment and monitoring, and glucose levels must be constantly monitored so that a diabetic can properly maintain a normal glucose levels and avoid the ill effects of diabetes. To this end, a variety of blood glucose monitoring devices has been developed to help people with diabetes maintain healthy levels of blood glucose. In some devices, a test strip is used to obtain a sample of blood for measurement of the glucose concentration in the sample. The test strip is then inserted into the blood glucose monitoring device, where the concentration of glucose in the blood is measured. The level is then interpreted as either within, above, or below a recommended level, so that the diabetic can take corrective action, if necessary.
Obtaining an accurate blood glucose reading is essential to those with diabetes. If the measurement is inaccurate, the user might take incorrect action to maintain proper blood glucose level, leading to a host of immediate and long-term health problems.
Unfortunately, many factors affect the blood glucose measurement and can cause inconsistent readings. One of these factors is hematocrit, the volume percentage of erythrocytes (red blood cells) in whole blood. See Dorland's Illustrated Medical Dictionary (1974).
Hematocrit levels affect the measurement of blood glucose in several ways. One way is through the effect of hematocrit on blood viscosity. Blood viscosity strongly correlates to hematocrit levels, as the greater the percentage of blood cells in the total blood volume, the more viscous the blood. The viscosity of blood then directly impacts glucose measurements, as these measurements are directly affected by the rate at which analytes and reagents diffuse within a sample chamber, and this rate of diffusion is inversely related to viscosity.
For example, in amperometric measurement methods (which measures the current being passed through a solution to determine the concentration of an analyte), low hematocrits are typically coupled to elevated glucose readings (and vice versa) for two reasons: (1) reduced viscosity increases the mobility of both glucose and the soluble reagents employed to react with it, and (2) reduced oxygen concentration lessens the percentage of electrons originating from glucose which ultimately are sidetracked to oxygen reduction. Both effects result in increased current, and therefore in elevated blood glucose readings. For high hematocrits, blood glucose readings are depressed, as (1) increased viscosity impedes the mobility of glucose as well as reacting strip reagents, and (2) additional glucose-derived electrons are shunted to oxygen.
More advanced testing techniques use coulometry, where the analyte concentration is determined by measuring the total charge consumed or produced during an electrolysis reaction. In coulometric methods, especially those employing an oxygen-insensitive enzyme, both the above sources of error are reduced. Nevertheless, coulometric methods may retain some hematocrit influence. Furthermore, as strip test times decrease to below 5 seconds, a further source of hematocrit dependence peculiar to coulometric methods may become significant. At very rapid test times, glucose stored inside the erythrocyte may not substantially diffuse out of the cell during the assay, leading to increased hematocrit influence.
Furthermore, hematocrit can vary significantly amongst individuals, which leads to inaccurate measurements of blood glucose in methods that provide a universal algorithm to correct for hematocrit dependence.
It is therefore desirable to know the hematocrit in a blood sample, so that a suitable correction can be applied to the blood glucose reading to increase its accuracy. Some efforts to measure hematocrit and correct blood glucose levels based on these measurements have been made; however, most current methods rely upon interelectrode impedance measurements. Impedance measurements are vulnerable to artifacts arising from incomplete filling and variations in electrode area and chamber thickness. Impedance measurements are also subject to interpersonal variation in blood conductivity due to non-hematocrit related effects such as varying salt concentrations. Additionally, to determine a hematocrit electrochemically, a second electrochemical measurement must be completed after the initial measurement for glucose concentration, which adds time to the testing process.
In addition, current technology typically requires a manual determination of whether the sample is of a control solution or a bodily fluid, such as blood. This can be problematic for several reasons; in particular, a patient's poor eyesight or lack of dexterity can make a manual selection to indicate whether the solution is a sample or control solution quite difficult. An error in this manual entry will result in an erroneous average, which can significantly affect a patient's choice of treatment options. For many patients, such manual intervention presents a substantial physical challenge. A distinct issue unrelated to the physical challenge of making such a manual adjustment, is that individuals who are responsible for showing their average glucose (a current function of most monitors) might willfully adjust their average glucose readings by using the low or normal glucose level control solution, and in this way lower, their average glucose level. Such a situation may be encountered when an individual's own actions would render the actual average glucose levels higher than desired. To further illustrate this example, when a teenager consumes food or beverages that violate a strict diet plan, he or she might be able to falsify the average glucose reading by substituting the blood sample with the low or normal glucose level control solution. Thus, manual determination of a control solution remains a substantial problem in patient care.
Therefore, what are needed are improved methods and devices for accurate measurement of blood glucose concentration and determination of a control solution. Of interest are methods and devices for measuring hematocrit in a sample to correct for hematocrit dependence.